Recently we have shown in both human disease and in pulmonary hypertension in the hypoxic rat that an early change, in the peripheral non-muscular regions of the pulmonary arterial tree, is the conversion of precursor cells to smooth muscle. These precursor cells are normally only identifiable ultrastructurally but in response to hypoxia, increase in size and become smooth muscle cells that are apparent by light microscopy. In these cells, the development of new intracellular organelles and contractile proteins will be followed by electron microscopy and immunofluorescence techniques. These techniques, with cell turnover studies, will establsh, for hilar and peripheral arteries, how hyperplasia/hypertrophy and differentiation from precursor cells contribute to increase in muscle. Since we have successfully established techniques for maintaining catheters indwelling in the pulmonary artery and aorta of rat, hemodynamic function can be measured from day to day. These measurements provide the basis for functional and structural correlation. Regression of structural changes and of pulmonary hypertension will be followed in both young and adult rats since their pressure differs. Human biopsy tissue from patients with congenital heart disease will also be studied by electron microscopic and immunofluescence techniques in order to establish the changes associated with pulmonary artery hypertension secondary to increased pulmonary blood flow. Previous work has been concerned either with the "acute" hypoxic resource, within hours, or with the "late chronic" response, after weeks; our studies are concerned mainly with the neglected period of 1 to 14 days, the developing or "early chronic" response. The intracellular structural changes explored here seem to be the basis for the sustained hypertensive response to hypoxia, and so are important to understanding its pathogenesis and are immediately applicable to clinical problems.